The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells

Michelle L Janas, Daniel Hodson, Zania Stamataki, Sue Hill, Katie Welch, Laure Gambardella, Lloyd C Trotman, Pier Paolo Pandolfi, Elena Vigorito, Martin Turner

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Control of the intracellular levels of phosphatidylinositol-(3, 4, 5)-trisphosphate by PI3K and phosphatase and tensin homolog (PTEN) is essential for B cell development and differentiation. Deletion of the PI3K catalytic subunit p110delta leads to a severe reduction in B1 and marginal zone (MZ) B cells, whereas deletion of PTEN results in their expansion. We have examined the relationship between these two molecules by generating mice with a B cell-specific deletion of PTEN (PTENB) and a concurrent germline deletion of p110delta. The expanded B1 cell population of PTENB mice was reduced to normal levels in PTENB/p110delta mutant mice, indicating a critical role for the p110delta isoform in the expansion of B1 cells. However, numbers of MZ B cells in the PTENB/p110delta mutants was intermediate between wild-type and PTENB-deficient mice, suggesting an additional role for other PI3K catalytic isoforms in MZ differentiation. Furthermore, the defective class switch recombination in PTENB B cells was only partially reversed in PTENB/p110delta double mutant B cells. These results demonstrate an epistatic relationship between p110delta and PTEN. In addition, they also suggest that additional PI3K catalytic subunits contribute to B cell development and function.
Original languageEnglish
Pages (from-to)739-46
Number of pages8
JournalJournal of Immunology
Volume180
Issue number2
Publication statusPublished - 15 Jan 2008

Keywords

  • Animals
  • PTEN Phosphohydrolase
  • Transgenes
  • Proto-Oncogene Proteins c-akt
  • Immunoglobulin Class Switching
  • Mice
  • B-Lymphocytes
  • Mice, Transgenic
  • Phosphatidylinositol 3-Kinases
  • Protein Isoforms
  • Gene Deletion
  • Lymphocyte Activation
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-2
  • Mice, Mutant Strains
  • Phosphorylation
  • Recombination, Genetic

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